The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer

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	The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer
	Zhou ZM 1,2; Liu R 2; Chen CS*1,2; chenc@mail.kiz.ac.cn
	2012
发表期刊	INTERNATIONAL JOURNAL OF CANCER
卷号	130 期号:7 页码:1504-1510
合作性质	其它
摘要	WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is an HECT domain-containing E3 ligase regulating apoptosis. The WWP1 gene is frequently amplified and overexpressed in estrogen receptor a (ERa)-positive breast cancer. Inhibition of WWP1 by siRNA induced apoptosis in MCF7 and HCC1500. In our study, we demonstrate that WWP1 depletion by siRNA activated the extrinsic apoptotic pathway. WWP1 depletion-induced apoptosis was rescued by the overexpression of the wild-type WWP1 but not the E3 ligase inactive WWP1-C890A mutant in MCF7 cells. In contrast, WWP1-C890A enhanced apoptosis, suggesting that the E3 ligase activity is required for WWP1 to promote cell survival. The expression levels of WWP1 in four breast cancer cell lines were specifically correlated with the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance, but not TNFa and doxorubicin resistance. Both WWP1 depletion and dominant negative WWP1 overexpression increased the TRAIL-induced caspase-8 recruitment and apoptosis although WWP1 did not regulate FLIP and death receptor levels. Depletion of the initial caspase-8 blocked WWP1 inhibition-induced apoptosis in MCF7. These findings suggest that inhibition of WWP1 may be combined with TRAIL to suppress ERa-positive breast cancer cell survival.
关键词	Wwp1 Trail Caspase-8 Apoptosis Breast Cancer
资助者	National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01
收录类别	SCI
语种	英语
资助者	National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01 ; National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01
WOS记录号	WOS:000299633300004
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/353002/6872
专题	科研部门_肿瘤生物学（陈策实）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	chenc@mail.kiz.ac.cn
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 2.The Center for Cell Biology and Cancer Research, MS355, Albany Medical College, Albany, NY
推荐引用方式 GB/T 7714	Zhou ZM,Liu R,Chen CS*,et al. The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer[J]. INTERNATIONAL JOURNAL OF CANCER,2012,130(7):1504-1510.
APA	Zhou ZM,Liu R,Chen CS*,&chenc@mail.kiz.ac.cn.(2012).The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer.INTERNATIONAL JOURNAL OF CANCER,130(7),1504-1510.
MLA	Zhou ZM,et al."The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer".INTERNATIONAL JOURNAL OF CANCER 130.7(2012):1504-1510.

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